{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:53:15Z","timestamp":1786593195070,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006379","name":"Office of Research and Development","doi-asserted-by":"publisher","award":["1IO1BX00788"],"award-info":[{"award-number":["1IO1BX00788"]}],"id":[{"id":"10.13039\/100006379","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"Objective<\/jats:title>Interstitial lung disease (ILD<\/jats:styled-content>) is a frequent complication of rheumatoid arthritis (RA<\/jats:styled-content>), occurring in up to 40% of patients during the course of their disease. Early diagnosis is critical, particularly given the shared clinicoepidemiologic features between advanced rheumatoid arthritis\u2013associated ILD<\/jats:styled-content> (RA<\/jats:styled-content>\u2010ILD<\/jats:styled-content>) and idiopathic pulmonary fibrosis (IPF<\/jats:styled-content>). This study was undertaken to define the molecular basis of this overlap through comparative profiling of serum proteins in RA<\/jats:styled-content>\u2010ILD<\/jats:styled-content> and IPF<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Multiplex enzyme\u2010linked immunosorbent assays (ELISA<\/jats:styled-content>s) were used to profile 45 protein biomarkers encompassing cytokines\/chemokines, growth factors, and matrix metalloproteinases (MMP<\/jats:styled-content>s) in sera obtained from RA<\/jats:styled-content> patients with ILD<\/jats:styled-content> and those without, individuals with IPF<\/jats:styled-content>, and healthy controls. Levels of selected serum proteins were compared between patient subgroups using adjusted linear regression, principal component analysis (PCA<\/jats:styled-content>), and least absolute shrinkage and selection operator (LASSO<\/jats:styled-content>) modeling.<\/jats:p><\/jats:sec>Results<\/jats:title>Multiplex ELISA<\/jats:styled-content>\u2010based assessment of sera from 2 independent cohorts (Veterans Affairs [VA] and Non\u2010VA<\/jats:styled-content>) revealed a number of non\u2010overlapping biomarkers distinguishing RA<\/jats:styled-content>\u2010ILD<\/jats:styled-content> from RA<\/jats:styled-content> without ILD<\/jats:styled-content> (RA<\/jats:styled-content>\u2013no ILD<\/jats:styled-content>) in adjusted regression models. Parallel analysis of sera from IPF<\/jats:styled-content> patients also yielded a discriminatory panel of protein markers in models adjusted for age\/sex\/smoking, which showed differential overlap with profiles linked to RA<\/jats:styled-content>\u2010ILD<\/jats:styled-content> in the VA<\/jats:styled-content> cohort versus the Non\u2010VA<\/jats:styled-content> cohort. PCA<\/jats:styled-content> revealed several distinct functional groups of RA<\/jats:styled-content>\u2010ILD<\/jats:styled-content>\u2013associated markers that, in the VA<\/jats:styled-content> cohort, encompassed proinflammatory cytokines\/chemokines as well as 2 different subsets of MMP<\/jats:styled-content>s. Finally, LASSO<\/jats:styled-content> regression modeling in the Non\u2010VA<\/jats:styled-content> and VA<\/jats:styled-content> cohorts revealed distinct biomarker combinations capable of discriminating RA<\/jats:styled-content>\u2010ILD<\/jats:styled-content> from RA<\/jats:styled-content>\u2013no ILD<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Comparative serum protein biomarker profiling represents a viable method for distinguishing RA<\/jats:styled-content>\u2010ILD<\/jats:styled-content> from RA<\/jats:styled-content>\u2013no ILD<\/jats:styled-content> and identifying population\u2010specific mediators shared with IPF<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41123","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T08:09:17Z","timestamp":1568794157000},"page":"409-419","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Comparative Profiling of Serum Protein Biomarkers in Rheumatoid Arthritis\u2013Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis"],"prefix":"10.1002","volume":"72","author":[{"given":"Daniel J.","family":"Kass","sequence":"first","affiliation":[{"name":"University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Nouraie","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn 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